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Masha Reider, Victoria Connaughton; Effects of embryonic thyroid inhibition on the development of the eye and retina. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3741.
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© ARVO (1962-2015); The Authors (2016-present)
Zebrafish eye development is a complex process that has been shown to be dependent on thyroid hormones (THs). The purpose of this study was to assess the effects of thyroid deprivation, using the goitrogenic thyroid inhibitor Methimazole (MMI), on the establishment of the eye and retinal layers in larval zebrafish. We used two temperatures (28°C and 31°C) to examine whether temperature and thyroid development interact during growth of the retina, a finding observed in overall morphological development.
Embryos (N=20) were placed in either control water or 0.3 mM MMI for each temperature group (N=4 beakers) between 0-1 hpf. Treated fish were removed from MMI at each subsampling period (hourly between 65-71hpf) and placed in control water until 72hpf, when all larvae were fixed. Cryosectioned tissues were stained with DAPI to assess retinal sections.
Temperature significantly affected development of eye size (p<0.001) and inter-eye distance (p<0.001). Peak inhibitory effects of MMI were observed between 66-68hpf, indicating an increased need for embryonic THs at this time. Analysis of the development of the ganglion cell layer (GCL), inner nuclear layer (INL), and inner plexiform layer (IPL) at 72 hpf revealed that MMI significantly affected the development of the GCL (p<0.05) such that untreated fish had thicker (vitread-sclerad direction) GCLs than treated fish, and were thicker when reared in 31°C than in 28°C. Treated fish displayed the opposite relationship: MMI-exposed larvae had a significantly thinner GCL when reared in 31°C. Similarly, IPL thickness was increased by the higher temperature (p<0.05) in both treated and control fish. INL thickness was also affected by temperature and MMI exposure (p<0.05) similar to trends observed for the GCL: a thicker INL was observed in fish reared in 31°C than in 28°C for control larvae, whereas treated fish reared in 31°C developed significantly smaller INLs than the low temperature group.
Overall, our results suggest differential sensitivity of the retina to MMI exposure and rearing temperature. The patterns found in GCL and INL development indicate THs and temperature interact during development of the eye and retina. Because MMI inhibits endogenous TH synthesis and not the use or supply of maternal T3/T4 from the yolk, sensitivity to this chemical suggests a need for THs in the development of the eye and retina between 65-71hpf.
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